The overall objective of this application is to confirm the identity of a possible autoantigen in antibiotic-resistant chronic Lyme arthritis. A small population of people infected with Borrelia Burgdorferi (Bb), the causative agent of Lyme disease, develop long term arthritis in one or more joints. Because: 1) The arthritis is not cured by long term use of antibiotics, 2) Many susceptible individuals are HLA-DRB10401 (DR4), and 3) T cells responding to both Bb surface antigen, Osp A and a human protein, hLFA-1, can be isolated from synovial fluid, an autoimmune etiology is suspected. Our first objective is to develop a model of chronic Lyme arthritis in mice by generating a transgenic (Tg) mouse line that expresses human. LFA-1, the suspected autoantigen as well as DR4. In these mice we will demonstrate that T cells specific for hLFA1 mediate chronic arthritis and can transfer disease to naive mice. Additionally we will generate fluorescently labeled hLFA-1332-343 and Osp A164-173 peptide-MHC tetramers that can bind and label T cells which express TCR specific for peptide. This will enable us to analyze whether the Osp A specific cell is also hLFA-1 specific, identifying a population of self-recognizing cross-reactive cells. We will transfer these human autoantigen specific cells into hLFA-1 TgDR4+/+ Beige-SCID mice and confirm their ability to generate arthritis. Data supporting an autoimmune etiology of chronic arthritis will allow physicians to begin treating this disease as an autoimmune rather than infectious disease.